Does Oxybutynin Alter Plaques, Amyloid Beta Peptides and Behavior in a Mouse Model of Alzheimer's Disease?

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In elderly patients oxybutynin (Sigma-Aldrich™) is commonly used to treat overactive bladder despite increased prevalence of Alzheimer's disease in this population. We determined whether oxybutynin altered plaque formation, amyloid β peptide expression and behavior in a transgenic mouse model of Alzheimer's disease expressing the mutant human presenilin 1 (DeltaE9) and a chimeric mouse/human amyloid precursor protein (APPswe).

Materials and Methods

Mice were treated for 30 days in an acute experiment or 5 months in a chronic experiment with oxybutynin (30 mg/kg) or vehicle. Behavioral testing was performed monthly with the elevated plus maze (Med Associates, St. Albans, Vermont) in the chronic experiment. Brains were tested for plaque burden using Hirano silver and thioflavin-S (Sigma-Aldrich) staining. Amyloid β peptide expression was tested using enzyme-linked immunosorbent assay for amyloid β peptides 1-40 and 1-42.


Animals treated with chronic oxybutynin had a decreased plaque burden in the hippocampus (mean ± SEM 2.2 ± 0.4 vs 4.1 ± 0.9 plaques, p <0.05) and cortex (5.8 ± 0.7 vs 11.6 ± 2.1, p <0.05) compared to animals treated with vehicle. Oxybutynin treated animals also had decreased expression of amyloid β 1-42 (82.8 ± 9.0 ηg/ml vs 105.6 ± 5.5 ηg/ml, p = 0.05) compared to animals treated with vehicle. Female Alzheimer's disease mice treated with oxybutynin but not males showed improved behavior with a greater percent of time spent in the closed arm or elevated plus maze (95.9% ± 1.6% vs 35.6% ± 18.9%, p <0.05). The greatest difference was noted at 3 months of treatment compared to vehicle.


These results suggest that oxybutynin may slow the progression of Alzheimer's disease in this model.

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